Functional basis of cleft lip liability in a-strain mice

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dc.contributor.advisorHallgrimsson, Benedikt
dc.contributor.advisorJirik, Frank
dc.contributor.authorSchmidt, Eric J
dc.date.accessioned2017-12-18T22:36:59Z
dc.date.available2017-12-18T22:36:59Z
dc.date.issued2012
dc.descriptionBibliography: p. 166-179en
dc.descriptionSome pages are in colour.en
dc.descriptionIncludes copy of animal protocol approvals and copyright permissions. Original copies with original Partial Copyright Licence.en
dc.description.abstractThe "facial shape hypothesis" holds that cleft lip penetrance rates among A-strain lines differ owing to subtle genetic differences in midfacial primordia size, orientation, and rates of growth-summarily "facial shape"-that place more liable lines closer to, and less liable Jines further from, a threshold shape value that is set by physical constraints limiting the range of shape variation tolerated before the primordia fail to contact or consolidate adequately into a unified structure separating the nasal slits from the mouth. Fixation for an IAP allele of Wnt9b, which plays a regulatory role in midfacial development, is a key component of the genetic liability. Variation in genetic maternal effects modifies penetrance rates through an unknown function. I tested the hypothesis that maternal background influences the rate clefted primary palates in litters by differentially shifting the distributions of Wnt9b IAP epigenetic modification toward an expression threshold set by a common level of tolerance for low Wnt9b expression in the developing upper jaw. IAP methylation profiles between a reciprocal pair of hybrids with a two-fold difference in liability did not substantially differ. Nor did a morphometric analysis suggest that genetic maternal effects differences influenced embryonic facial shape. The data imply a role for maternal effects variation impacting palatogenesis via a mechanism outside epigenetic modification of the Wnt9b IAP but also independent of normal variations in midfacial shape with respect to a shape threshold. The significance of the alternative "two state" hypothesis, holding that penetrance rate differences among the A-strain are a function of the rate at which somatic differences arise between normal and cleft penetrant embryos, is considered.
dc.format.extentxv, 179 leaves : ill. ; 30 cm.en
dc.identifier.citationSchmidt, E. J. (2012). Functional basis of cleft lip liability in a-strain mice (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/5025en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/5025
dc.identifier.urihttp://hdl.handle.net/1880/106026
dc.language.isoeng
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.titleFunctional basis of cleft lip liability in a-strain mice
dc.typedoctoral thesis
thesis.degree.disciplineMedical Science
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
ucalgary.thesis.accessionTheses Collection 58.002:Box 2119 627942989
ucalgary.thesis.notesUARCen
ucalgary.thesis.uarcreleaseyen
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